{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:43:57Z","timestamp":1777524237845,"version":"3.51.4"},"reference-count":21,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00 DE022378, R37 DE-08559, DE-016148"],"award-info":[{"award-number":["R00 DE022378, R37 DE-08559, DE-016148"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The Cleft Palate Craniofacial Journal"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Cleft lip and\/or cleft palate (CL\/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL\/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Method:<\/jats:title>\n                    <jats:p>We resequenced DNA from 397 sub-Saharan Africans with CL\/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL\/P literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL\/P.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1055665618754948","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T14:40:33Z","timestamp":1519828833000},"page":"736-742","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel\n                    <i>GREM1<\/i>\n                    Variations in Sub-Saharan African Patients With Cleft Lip and\/or Cleft Palate"],"prefix":"10.1177","volume":"55","author":[{"given":"Lord Jephthah Joojo","family":"Gowans","sequence":"first","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganiyu","family":"Oseni","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Ladoke Akintola University of Science and Technology, Osogbo, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Mossey","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University of Dundee, Dundee, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasiu Lanre","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mekonen A.","family":"Eshete","sequence":"additional","affiliation":[{"name":"Addis Ababa University, School of Public Health, Addis Ababa, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara D.","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Donkor","sequence":"additional","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solomon","family":"Obiri-Yeboah","sequence":"additional","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyikua","family":"Plange-Rhule","sequence":"additional","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Oti","sequence":"additional","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-2976","authenticated-orcid":false,"given":"Arwa","family":"Owais","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Olaitan","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Ladoke Akintola University of Science and Technology, Osogbo, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babatunde S.","family":"Aregbesola","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadekemi O.","family":"Oginni","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seidu A.","family":"Bello","sequence":"additional","affiliation":[{"name":"State House Clinic, Abuja, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Audu","sequence":"additional","affiliation":[{"name":"Department of Virology, Nigerian Institute of Medical Research, Lagos, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chika","family":"Onwuamah","sequence":"additional","affiliation":[{"name":"Department of Virology, Nigerian Institute of Medical Research, Lagos, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pius","family":"Agbenorku","sequence":"additional","affiliation":[{"name":"Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mobolanle O.","family":"Ogunlewe","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukman O.","family":"Abdur-Rahman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Ilorin, Ilorin, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary L.","family":"Marazita","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. A.","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azeez","family":"Butali","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"bibr1-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23244"},{"key":"bibr2-1055665618754948","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9503.1"},{"key":"bibr3-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.110"},{"key":"bibr4-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36691"},{"key":"bibr5-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.66"},{"key":"bibr6-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1597\/10-133"},{"key":"bibr7-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"bibr8-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31541"},{"key":"bibr9-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516657003"},{"key":"bibr10-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2263"},{"key":"bibr11-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1754-7"},{"key":"bibr12-1055665618754948","first-page":"2862","volume":"25","author":"Leslie EJ","year":"2016","journal-title":"Hum Mol Genet"},{"key":"bibr13-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.014"},{"key":"bibr14-1055665618754948","first-page":"12","volume":"1005914","author":"Ludwig KU","year":"2016","journal-title":"PLoS Genet"},{"key":"bibr15-1055665618754948","first-page":"829","volume":"26","author":"Ludwig KU","year":"2017","journal-title":"Hum Mol Genet"},{"key":"bibr16-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1038\/ng.506"},{"key":"bibr17-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1159\/000337464"},{"key":"bibr18-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23391"},{"key":"bibr19-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.02.002"},{"key":"bibr20-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1159\/000015568"},{"key":"bibr21-1055665618754948","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14364"}],"container-title":["The Cleft Palate Craniofacial Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1055665618754948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1055665618754948","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1055665618754948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:23:00Z","timestamp":1777393380000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1055665618754948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,28]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1177\/1055665618754948"],"URL":"https:\/\/doi.org\/10.1177\/1055665618754948","relation":{},"ISSN":["1055-6656","1545-1569"],"issn-type":[{"value":"1055-6656","type":"print"},{"value":"1545-1569","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,28]]}}}